The pathological mechanism resulting in B cell chronic lymphocytic leukemia (B-CLL), the most common leukemia in the Western world, remains unidentified. Common to B-CLL are specific chromosomal deletions, presumably resulting in the loss of tumor suppressor genes. The most common deletion, Ch13q14, contains the putative methyltransferase enzyme Setdb2. Setdb2 is expressed in B cells and has been implicated in immunoglobulin production. Based on domain structures, Setdb2 is predicted to elicit methyltransferase and DNA binding activity, and thus act as an epigenetic modifier. As deregulation of several methyltransferase enzymes promotes oncogenesis, we propose the loss of the Setdb2 gene contributes to the onset of B-CLL. To test this, mice containing a B cell conditional, targeted deletion of Setdb2 will be generated and analyzed for signs of B cell leukemia. Furthermore, Setdb2 binding regions throughout the genome of B cells will be identified using ChlP-on-chip analysis. Lastly, the Setdb2 methyltransferase activity and B cell expression pattern will be characterized to further understand Setdb2 function. Overall, this study may provide insights into the pathology of B-CLL, while furthering our understanding of epigenetic control of B cell differentiation.